Fecal and Tissue Microbiota Are Associated with Tumor T-Cell Infiltration and Mesenteric Lymph Node Involvement in Colorectal Cancer.

Colorectal cancer (CRC) is associated with alterations of the fecal and tissue-associated microbiome. Preclinical models support a pathogenic role of the microbiome in CRC, including in promoting metastasis and modulating antitumor immune responses. To investigate whether the microbiome is associated with lymph node metastasis and T cell infiltration in human CRC, we performed 16S rRNA gene sequencing of feces, tumor core, tumor surface, and healthy adjacent tissue collected from 34 CRC patients undergoing surgery (28 fecal samples and 39 tissue samples). Tissue microbiome profiles-including increased Fusobacterium-were significantly associated with mesenteric lymph node (MLN) involvement. Fecal microbes were also associated with MLN involvement and accurately classified CRC patients into those with or without MLN involvement. Tumor T cell infiltration was assessed by immunohistochemical staining of CD3 and CD8 in tumor tissue sections. Tumor core microbiota, including members of the Blautia and Faecalibacterium genera, were significantly associated with tumor T cell infiltration. Abundance of specific fecal microbes including a member of the Roseburia genus predicted high vs. low total and cytotoxic T cell infiltration in random forests classifiers. These findings support a link between the microbiome and antitumor immune responses that may influence prognosis of locally advanced CRC.

Patient-Centered Decision-making for Postoperative Narcotic-Free Endocrine Surgery: A Randomized Clinical Trial.

Importance: Historically, opioid pain medications have been overprescribed following thyroid and parathyroid surgery. Many narcotic prescriptions are incompletely consumed, creating waste and opportunities for abuse. Objective: To determine whether limiting opioid prescriptions after outpatient thyroid and parathyroid surgery to patients who opt in to narcotic treatment reduces opioid consumption without increasing postoperative pain compared with usual care (routine narcotic prescriptions). Design, Setting, and Participants: A randomized clinical trial of Postoperative Opt-In Narcotic Treatment (POINT) or routine narcotic prescription (control) was conducted at a single tertiary referral center from June 1 to December 30, 2020. A total of 180 adults undergoing ambulatory cervical endocrine surgery, excluding patients currently receiving opioids, were assessed for eligibility. POINT patients received perioperative pain management counseling and were prescribed opioids only on patient request. Patients reported pain scores (0-10) and medication use through 7 daily postoperative surveys. Logistic regression was used to determine factors associated with opioid consumption. Interventions: Patients in the POINT group were able to opt in or out of receiving prescriptions for opioid pain medication on discharge. Control patients received routine opioid prescriptions on discharge. Main Outcomes and Measures: Daily peak pain score through postoperative day 7 was the primary outcome. Noninferiority was defined as a difference less than 2 on an 11-point numeric rating scale from 0 to 10. Analysis was conducted on the evaluable population. Results: Of the 180 patients assessed for eligibility, the final study cohort comprised 102 patients: 48 randomized to POINT and 54 to control. Of these, 79 patients (77.5%) were women and median age was 52 (interquartile range, 43-62) years. A total of 550 opioid tablets were prescribed to the control group, and 230 tablets were prescribed to the POINT group, in which 23 patients (47.9%) opted in for an opioid prescription. None who opted out subsequently required rescue opioids. In the first postoperative week, 17 POINT patients (35.4% of survey responders in the POINT group) reported consuming opioids compared with 27 (50.0%) control patients (P = .16). Median peak outpatient pain scores were 6 (interquartile range, 4-8) in the control group vs 6 (interquartile range, 5-7) in the POINT group (P = .71). In multivariate analysis, patients with a history of narcotic use were 7.5 times more likely to opt in (95% CI, 1.61-50.11; P = .02) and 4.8 times more likely to consume opioids (95% CI, 1.04-1.52; P = .01). Higher body mass index (odds ratio, 1.11; 95% CI, 1.01-1.23; P = .03) and highest inpatient postoperative pain score (odds ratio, 1.24; 95% CI, 1.04-1.52; P = .02) were also associated with opioid consumption. Conclusions and Relevance: In this trial, an opt-in strategy for postoperative narcotics reduced opioid prescription without increasing pain after cervical endocrine surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04710069.

Anal Sphincteroplasty in the Minimally Invasive Era: Assessment of National Trends and Complications.

Fecal incontinence is a debilitating and underreported condition. Despite introduction of novel therapies in recent years, anal sphincteroplasty (AS) remains the surgical choice for certain patients. Previous reports have primarily focused on single-surgeon or single-center experience with AS. The purpose of this study was to assess patient characteristics and perioperative outcomes of AS using a national cohort. Patients (n = 586) who underwent AS as a primary procedure between 2009 and 2015 were identified by the CPT code as recorded in the study and were evaluated and examined for association with 30-day complications. The number of sphincteroplasties performed decreased seven-fold between 2009 and 2015. Wound infection, wound dehiscence, and urinary tract infection were the most common complications, occurring in 30 (5.1%), 12 (2.1%), and 6 (1%) patients, respectively. Preoperative steroid use and surgeon specialty were associated with wound complications on multivariate analysis. We present the first national study of patients undergoing AS and identify factors that predispose to wound complications. In addition, we demonstrate that the number of anal sphincteroplasties performed in the United States is decreasing dramatically, likely because of novel therapy for fecal incontinence. We hope that this study will assist in patient counseling and call attention to preserving surgical training as utilization of AS rapidly declines.

Application of a newly designed microfork probe for robotic-guided pelvic intraoperative neuromapping.

Introduction: Robotic-assisted total mesorectal excision (TME) with pelvic intraoperative neuromapping was recently accomplished. However, neuromapping is conventionally conducted by a hand-guided laparoscopic probe. We introduce a prototype microfork probe to make robotic-guided neuromapping feasible. Experiments and Technical Setup: Two porcine experiments with nerve-sparing TME surgery were performed. A newly designed prototype bipolar microfork probe was inserted intraabdominally and guided with the robotic forceps. Intermittent neuromapping was then conducted and neuromonitoring data integrated in the surgeon console viewer. Conclusion: Robotic-guided neuromapping is shown to be feasible and fully controllable from the surgeon console.

Obesity Is Associated with Early Onset of Gastrointestinal Cancers in California.

Background: Although it is well known that obesity is a risk factor for gastrointestinal (GI) cancer, it is not well established if obesity can cause earlier GI cancer onset. Methods: A cross-sectional study examining the linked 2004-2008 California Cancer Registry Patient Discharge Database was performed to evaluate the association between obesity and onset age among four gastrointestinal cancers, including esophageal, gastric, pancreatic, and colorectal cancers. Regression models were constructed to adjust for other carcinogenic factors. Results: The diagnosis of obesity (BMI > 30) was associated with a reduction in diagnosis age across all four cancer types: 3.25 ± 0.53 years for gastric cancer, 4.56 ± 0.18 years for colorectal cancer, 4.73 ± 0.73 years for esophageal cancer, and 5.35 ± 0.72 for pancreatic cancer. The diagnosis of morbid obesity (BMI > 40) was associated with a more pronounced reduction in the age of diagnosis: 5.48 ± 0.96 years for gastric cancer, 7.75 ± 0.30 years for colorectal cancer, 7.67 ± 1.26 years for esophageal cancer, and 8.19 ± 1.25 years for pancreatic cancer. Both morbid obesity and obesity remained strongly associated with earlier cancer diagnosis for all four cancer types even after adjusting for other available cancer risk factors. Conclusions: The diagnosis of obesity, especially morbid obesity, was associated with a significantly earlier gastrointestinal cancer onset in California. Further research with prospective cohort data may be required to establish the causal relationship between obesity and cancer onset age.

Racial Disparities in the Incidence of Pulmonary Embolism after Colectomy.

Disparities in the incidence of pulmonary embolism (PE) based on racial and socioeconomic factors remain ill-defined. The present study evaluated the impact of race and hospital characteristics on rates of PE for all adult colectomy patients in the 2005 to 2014 Nationwide Inpatient Sample. Hospitals were designated as high-burden hospitals (HBHs) or low-burden hospitals of underinsured payers. Chi-squared tests of trend and multivariable regression adjusting for patient and hospital characteristics were performed. Of the 2,737,977 adult patients who underwent colectomy in the study period, 79 per cent were White, 10 per cent Black, and 7 per cent Hispanic. The annual rate of PE increased from 0.6 per cent in 2005 to 0.95 per cent in 2014 (P < 0.0001). Black patients had significantly higher incidence of PE than Whites (1.5% vs 0.9%, P < 0.001) and Hispanics (1.5% vs 0.8%, P < 0.001). Colectomy at HBHs was also associated with significantly higher rates of PE (1% vs 0.86%, P < 0.001). After adjusting for baseline differences, colectomy at HBHs (odds ratio 1.14, 95% confidence interval 1.02-1.27, P = 0.02) and Black race (odds ratio 1.4, 95% confidence interval 1.26-1.66, P < 0.001) were independent predictors of PE. In this national study of colectomy patients, Black patients experienced a disproportionate burden of postoperative PE. Further investigation into the causes and prevention of PE in vulnerable populations may identify targets for surgical quality improvement.

Point/Counterpoint: Are Outstanding Leaders Born or Made?

The question of whether outstanding leaders are born or made has been debated for years. There are numerous examples of historical figures that came naturally to leadership, while others developed their leadership skills through tenacity and experience. To understand leadership, both nature (the genetic component) and nurture (the environmental influences) must be considered. This article represents the work of two Academic Leadership Fellows Program groups who debated each position at the 2016 American Association of Colleges of Pharmacy (AACP) Interim Meeting in Tampa, Fla., in February 2016.

Wireless Technology to Track Surgical Patients after Discharge: A Pilot Study.

Failure to detect changes in patients' postoperative health status increases the risk of adverse outcomes, including complications and readmission. We sought to design and implement a real-time surveillance system for postoperative colorectal surgery patients using wireless health technology. Participants were assigned a preprogrammed tablet computer during their inpatient hospitalization, and asked to complete a daily survey regarding their postoperative health status until their first clinic visit. Surveys were transmitted wirelessly to a secure database for review. As a pilot study, we report on our first 20 consecutively enrolled patients, monitored for 265 patient days. Overall compliance was 63 per cent (data available for 166 of the 265 days), but varied by patient from 26 to 100 per cent. We were able to reliably collect basic data on postoperative health status as well as patient-reported outcomes not previously captured by standard assessment techniques. Qualitative data suggest that the experience strengthened patients' relationship with their surgeon and aided in their recovery. Postoperative remote monitoring is feasible, and provides more detailed and complete information to the clinical team. Wireless health technology represents an opportunity to close the information gap between discharge and first clinic visit, and, eventually, to improve patient-provider communication, increase patient satisfaction, and prevent unnecessary readmissions.

A single institution experience in compliance with universal screening for Lynch syndrome in colorectal cancer.

BACKGROUND: Detection of Lynch syndrome has the potential to reduce morbidity and mortality among patients and their family members due to beneficial screening and treatment options. Several institutions have begun to adopt universal rather than risk-stratified screening protocols, but the lack of 100 % compliance rates requires identification of system-level interventions to improve screening practices. OBJECTIVE: We aimed to identify patient, tumor, and system factors associated with lack of screening and identify system-based interventions to improve Lynch syndrome screening. DESIGN AND SETTINGS: This study is a retrospective analysis of Lynch syndrome screening among colorectal cancer patients undergoing surgery in a single healthcare system. PATIENTS: Two hundred and sixty-two patients who underwent surgery for colorectal cancer were studied. MAIN OUTCOME MEASURES: Rate of Lynch syndrome screening. RESULTS: We identified that 75 % of the total cohort was screened for Lynch syndrome. Of patients under the age of 50, 78 % percent were screened. Lower screening rates were found among patients with complete pathologic tumor response and lower pathologic stage of tumor. Higher screening rates were found at the academic hospital and with colorectal surgeons. In multivariable logistic regression analysis, lower screening rates were associated with community hospital location (OR, 0.22; 95 % CI, 0.08-0.56). LIMITATIONS: Results may not be generalizable to different hospital settings. CONCLUSIONS: Several potential system-level interventions were identified to improve screening rates including an emphasis on improved provider communication.

Preventable readmissions to surgical services: lessons learned and targets for improvement.

BACKGROUND: Hospital readmissions are under intense scrutiny as a measure of health care quality. The Center for Medicare and Medicaid Services (CMS) has proposed using readmission rates as a benchmark for improving care, including targeting them as nonreimbursable events. Our study aim was to describe potentially preventable readmissions after surgery and to identify targets for improvement. STUDY DESIGN: Patients discharged from a general surgery service over 8 consecutive quarters (Q4 2009 to Q3 2011) were selected. A working group of attending surgeons defined terms and created classification schemes. Thirty-day readmissions were identified and reviewed by a 2-physician team. Readmissions were categorized as preventable or unpreventable, and by target for future quality improvement intervention. RESULTS: Overall readmission rate was 8.3% (315 of 3,789). The most common indication for initial admission was elective general surgery. Among readmitted patients in our sample, 28% did not undergo an operation during their index admission. Only 21% (55 of 258) of readmissions were likely preventable based on medical record review. Of the preventable readmissions, 38% of patients were discharged within 24 hours and 60% within 48 hours. Dehydration occurred more frequently among preventable readmissions (p < 0.001). Infection accounted for more than one-third of all readmissions. Among preventable readmissions, targets for improvement included closer follow-up after discharge (49%), management in the outpatient setting (42%), and avoidance of premature discharge (9%). CONCLUSIONS: A minority of readmissions may potentially be preventable. Targets for reducing readmissions include addressing the clinical issues of infection and dehydration as well as improving discharge planning to limit both early and short readmissions. Policies aimed at penalizing reimbursements based on readmission rates should use clinical data to focus on inappropriate hospitalization in order to promote high quality patient care.

Evaluation of hospital readmissions in surgical patients: do administrative data tell the real story?

IMPORTANCE: The Centers for Medicare & Medicaid Services has developed an all-cause readmission measure that uses administrative data to measure readmission rates and financially penalize hospitals with higher-than-expected readmission rates. OBJECTIVES: To examine the accuracy of administrative codes in determining the cause of readmission as determined by medical record review, to evaluate the readmission measure's ability to accurately identify a readmission as planned, and to document the frequency of readmissions for reasons clinically unrelated to the original hospital stay. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of all consecutive patients discharged from general surgery services at a tertiary care, university-affiliated teaching hospital during 8 consecutive quarters (quarter 4 [October through December] of 2009 through quarter 3 [July through September] of 2011). Clinical readmission diagnosis determined from direct medical record review was compared with the administrative diagnosis recorded in a claims database. The number of planned hospital readmissions defined by the readmission measure was compared with the number identified using clinical data. Readmissions unrelated to the original hospital stay were identified using clinical data. MAIN OUTCOMES AND MEASURES: Discordance rate between administrative and clinical diagnoses for all hospital readmissions, discrepancy between planned readmissions defined by the readmission measure and identified by clinical medical record review, and fraction of hospital readmissions unrelated to the original hospital stay. RESULTS: Of the 315 hospital readmissions, the readmission diagnosis listed in the administrative claims data differed from the clinical diagnosis in 97 readmissions (30.8%). The readmission measure identified 15 readmissions (4.8%) as planned, whereas clinical data identified 43 readmissions (13.7%) as planned. Unrelated readmissions comprised 70 of the 258 unplanned readmissions (27.1%). CONCLUSIONS AND RELEVANCE: Administrative billing data, as used by the readmission measure, do not reliably describe the reason for readmission. The readmission measure accounts for less than half of the planned readmissions and does not account for the nearly one-third of readmissions unrelated to the original hospital stay. Implementation of this readmission measure may result in unwarranted financial penalties for hospitals.

Diverticulitis occurs early after lung transplantation.

BACKGROUND: Lung transplantation recipients are at an increased risk for developing diverticulitis. However, the incidence and natural history of diverticulitis have not been well characterized. Our objective was to identify patient and transplant-related factors that may be associated with an increased risk of developing diverticulitis in this patient population. MATERIALS AND METHODS: This is a retrospective single institution study. All patients who received a lung transplant between May 2008 and July 2013 were evaluated using an existing lung transplantation database. Patient-related factors, the incidence and timing of diverticulitis, and outcomes of medical and surgical management were measured. RESULTS: Of the 314 patients who received a lung transplant, 14 patients (4.5%) developed diverticulitis. All episodes (100%) of diverticulitis occurred within the first 2 y after transplantation. Eight patients (57%) required surgery with a mortality rate of 12.5%. Six patients (43%) were managed medically and did not require surgery with a mean follow-up period of 442 d. CONCLUSIONS: Diverticulitis is common after lung transplantation and occurs with a higher incidence compared with the general population. Diverticulitis occurs early in the posttransplant period, and the majority of patients require surgery. Patients who respond promptly to medical treatment may not require elective resection. A greater awareness of the risk of diverticulitis in the early posttransplant period may allow for earlier diagnosis and treatment.

Team-based learning in US colleges and schools of pharmacy.

OBJECTIVE: To characterize the use of team-based learning (TBL) in US colleges and schools of pharmacy, including factors that may affect implementation and perceptions of faculty members regarding the impact of TBL on educational outcomes. METHODS: Respondents identified factors that inhibit or enable TBL use and its impact on student learning. Results were stratified by type of institution (public/private), class size, and TBL experience. RESULTS: Sixty-nine of 100 faculty members (69%) representing 43 (86%) institutions responded. Major factors considered to enable TBL implementation included a single campus and student and administration buy-in. Inhibiting factors included distant campuses, faculty resistance, and lack of training. Compared with traditional lectures, TBL is perceived to enhance student engagement, improve students' preparation for class, and promote achievement of course outcomes. In addition, TBL is perceived to be more effective than lectures at fostering learning in all 6 domains of Bloom's Taxonomy. CONCLUSIONS: Despite potential implementation challenges, faculty members perceive that TBL improves student engagement and learning.

Combined endoscopic and laparoscopic surgery may be an alternative to bowel resection for the management of colon polyps not removable by standard colonoscopy.

BACKGROUND: Benign colon polyps may require bowel resection if endoscopic polypectomy cannot be performed to assess adequately for cancer. However, endoscopic removal still may be possible using combined endoscopic and laparoscopic surgery (CELS). The CELS procedure allows for intra- and extraluminal manipulation of the bowel wall to facilitate polyp removal, thereby avoiding bowel resection. This study evaluated the authors' institutional experience with CELS in this patient population. METHODS: Between August 2008 and October 2012, all patients referred to undergo surgery for a benign colon polyp were retrospectively reviewed for operative characteristics, pathology, and postoperative outcomes. Of 14 patients, five were considered candidates for CELS and were compared with nine patients who underwent resection. RESULTS: The average patient age was similar between the two groups (CELS, 64.9 years vs. resection, 68.3 years). The mean polyp size was 2.3 cm in the CELS group and 2.9 cm in the resection group. In the CELS group, polyps were successfully removed in all cases. The mean operating room time was 159 min in the CELS group and 205 min in the resection group. The median hospital stay was 1 day in the CELS group and 5 days in the resection group. No complications occurred in the CELS group. Two patients in the resection group (22 %) experienced a wound infection. One patient had a postoperative ileus (11 %). Four patients in the CELS group had a benign adenoma. One patient had a benign frozen section evaluation, but the final pathology showed adenocarcinoma requiring a subsequent colectomy. In the resection group, six patients had a benign adenoma, and three patients had a T1N0 cancer. In the CELS group, repeat endoscopy was performed an average of 9.9 months after CELS. Two patients had a residual polyp, and two patients had new polyps in a different location. All were successfully removed. CONCLUSION: For benign-appearing polyps not amenable to endoscopic techniques alone, CELS may be an alternative to formal bowel resection for carefully selected patients. The CELS procedure can be performed safely with minimal morbidity and with outcomes that compare favorably with those of formal colectomy.

Fast-track pathways in colorectal surgery.

Enhanced recovery after surgery or "fast-track" pathways are a multimodal approach to the perioperative management of patients undergoing colorectal surgery designed to improve the overall quality of care. These pathways use existing evidence to streamline and standardize the perioperative management of patients to improve pain management, speed intestinal recovery, and ultimately facilitate a more rapid hospital discharge, thus minimizing complications, decreasing the use of hospital resources and health care costs, and improving overall patient care and satisfaction. Fast-track protocols are safe for patients and offer improvement in intestinal recovery and hospital discharge.

Is an elective diverting colostomy warranted in patients with an endoscopically obstructing rectal cancer before neoadjuvant chemotherapy?

BACKGROUND: Many surgeons prefer immediate diversion in patients with endoscopically obstructed rectal cancer before starting neoadjuvant chemotherapy. OBJECTIVE: The aim of this study was to compare immediate neoadjuvant chemoradiotherapy with diversion for endoscopically obstructed rectal cancer. DESIGN: This study is a retrospective review of patients with rectal adenocarcinoma treated from January 2000 to December 2009. Demographic, tumor, treatment, and outcome data were obtained. Data were analyzed by the use of the Fisher exact probability test and the Student t test. SETTINGS: This study was conducted at a tertiary care hospital/referral center. PATIENTS: Included were patients with a rectal adenocarcinoma unable to be traversed endoscopically but without clinical evidence of obstruction before the initiation of neoadjuvant chemoradiotherapy. Patients with recurrent tumors or those who did not complete neoadjuvant chemoradiotherapy because of compliance were excluded. MAIN OUTCOME MEASURES: The primary outcomes measured were the interval from diagnosis to neoadjuvant chemoradiotherapy initiation and resection and the incidence of complete obstruction. RESULTS: Eighty-five patients with endoscopically obstructed rectal cancer were identified; 16 underwent immediate diversion before neoadjuvant chemoradiotherapy (diverted group) and 69 were treated with immediate neoadjuvant chemoradiotherapy. Five patients undergoing immediate neoadjuvant chemoradiotherapy presented with bloating and distension; 2 were treated with dietary modification, and 3 (4.3%) progressed to complete obstruction following completion of neoadjuvant chemoradiotherapy and required diversion. Both groups were similar in age, tumor height, and surgical margin status. Patients undergoing diversion required a significantly greater number of permanent stomas and were associated with a higher rate of radical pelvic surgery. There was a significant delay in the initiation of neoadjuvant chemoradiotherapy (p < 0.05) and proctectomy (p < 0.001) from the time of diagnosis in the diverted group compared with the immediate neoadjuvant chemoradiotherapy group. The tumors of patients undergoing diversions were more likely to be unresectable following neoadjuvant chemoradiotherapy. LIMITATIONS: This study was limited by its retrospective design and possible selection bias. CONCLUSIONS: Immediate diversion is unnecessary in endoscopically obstructed rectal cancer without clinical signs of obstruction. There appears to be a relationship between immediate diversion and delay in initiation of neoadjuvant chemoradiotherapy and proctectomy. We conclude that immediate neoadjuvant chemoradiotherapy in patients with endoscopically obstructed rectal cancer is safe and feasible.

Clinically enlarged lateral pelvic lymph nodes do not influence prognosis after neoadjuvant therapy and TME in stage III rectal cancer.

PURPOSE: The significance of lateral pelvic lymph nodes (LPLN) in rectal cancer remains unclear. The purpose of this study was to determine the outcome of patients with LPLNs identified on pretherapy imaging who were treated with neoadjuvant therapy followed by proctectomy without LPLN dissection. METHODS: Pretherapy imaging of patients with stage III rectal cancer was reviewed to determine perirectal and LPLN enlargement. Data were collected on preoperative therapy, operative resection, adjuvant therapy, and patient outcomes and were correlated to the presence or absence of preoperatively identified LPLNs (LPLN+ and LPLN-). RESULTS: Of the 53 patients identified who were treated between 2000 and 2005, 30 (57%) were LPLN+ on preoperative imaging. All patients received preoperative radiation therapy and total mesorectal excision. The local recurrence was 13%, and there was no difference related to LPLN status. A comparison of the overall and disease-free survival in patients with and without enlarged LPLNs revealed no difference. CONCLUSIONS: The LPLNs that were identified on pretherapy imaging do not affect the overall or disease-free survival after the neoadjuvant therapy and proctectomy in stage III rectal cancer. A lateral pelvic lymph node dissection does not appear to be justified in stage III patients with LPLNs on pretherapy imaging who receive neoadjuvant therapy.

Predictive clinicopathologic factors for limited response of T3 rectal cancer to combined modality therapy.

PURPOSE: The response of T3 rectal cancer to combined modality therapy (CMT) is highly predictive of long-term outcome following surgery. The aim of this study was to identify pretreatment factors associated with poor tumor response to neoadjuvant chemoradiation. METHODS: A prospective institutional database at Memorial Sloan-Kettering Cancer Center was queried for endorectal ultrasound (ERUS) stage T3N0-2 rectal cancer patients, treated with CMT followed by surgical resection, between 1998 and 2003. Preoperative clinicopathologic factors determined by biopsy, ERUS, proctoscopy, and digital rectal examination were correlated with the degree of downstaging of the primary mural lesion (tumor downstaging) in response to neoadjuvant therapy. Associations were analyzed by chi-square, Kaplan-Meier, and logistic regression. RESULTS: Of 274 patients, 51% obtained tumor downstaging in response to preoperative treatment, i.e., lower pathologic T-stage compared with pretreatment ERUS. Five-year recurrence-free survival was 89% in the cohort that obtained tumor downstaging compared with only 45% in the cohort that obtained no tumor downstaging. Factors significantly associated with limited or lack of tumor downstaging after CMT included: fixed tumor on digital rectal examination (p < 0.021), near-circumferential tumor (p < 0.011), tumor stenosis (p < 0.025), metastatic disease (p < 0.012), biopsy-proven poorly differentiated pathology (p < 0.002), and radial extension >2.5 mm on ERUS (p < 0.031). On multivariate analysis, deep radial extension on ERUS, metastatic disease, and poorly differentiated pathology were in each, independently associated with limited or lack of tumor downstaging. CONCLUSIONS: Pretreatment evaluation with biopsy, proctoscopy, and ERUS can identify T3 rectal cancer patients unlikely to respond well to CMT. These patients may be considered for alternative protocols and their tumors studied to ascertain the molecular events responsible for resistance to chemoradiation.